The research outlined in this proposal will examine mechanistic aspects of the enzymatic head-to-tail and head-to-head terpene condensation reactions. We will synthesize three types of substrate analogs (3-trifluoromethylprenyl pyrophosphates, 2-fluoroisopentenyl pyrophosphate, and thiopyrophosphate derivatives of prenols and presqualene alcohol) to test as substrates for prenyl transferase (FPP synthetase) and squalene synthetase. The substrates are designed to respond differently depending on mechanism. From inhibition studies (competitive and non-competitive) we should be able to elucidate the mechanisms of these important biological reactions. Specific regulation of terpene condensations is not possible with present technology but may be feasible with our substrate analogs. Potential applications of our results are selective regulation of sterol synthesis and synthesis of bacterial cell walls.